Researchers from Mount Sinai School of Medicine are presenting important discoveries on the involvement of the immune system and dopamine cells in the onset of depression at Neuroscience 2012, the Society for Neuroscience’s 42nd annual meeting on October 13 -17 in New Orleans.

In addition to scientists presenting at the conference, Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Mount Sinai School of Medicine, Executive Vice President for Academic Affairs, The Mount Sinai Medical Center, is available to speak about depression and the psychobiological mechanisms of human resistance to stress. As a renowned expert in the neurobiology and treatment of mood and anxiety disorders, he has led research teams that have discovered that ketamine is a rapidly-acting drug in patients with treatment-resistant depression.

Dr. Charney has co-authored a book, Resilience: The Science of Mastering Life’s Greatest Challenges, and a recent review article on this topic is featured in this week’s issue of the journal Science, found here. The website also includes a podcast on how resilience training may help as a treatment for depression.

Led by Dipesh Chaudhury, PhD, Associate Scientist, and Jessica Walsh, MSc, in the laboratory of Ming-Hu Han, PhD, in the Department of Pharmacology and Systems Therapeutics at Mount Sinai, researchers evaluated the activity of dopamine neurons in the ventral tegmental area, the brain’s reward center. These neurons produce the brain’s dopamine, a chemical that regulates reward-seeking behavior.

To assess whether inhibiting dopamine neurons affected depression, the research team modulated dopamine cell activity in mice using a novel technique called optogenetics. Optogenetics allows scientists to engineer molecules that can be targeted to specific neurons, in this case dopamine neurons, and increase or decrease their activity using light.

By increasing the activity of dopamine neurons in already-stressed mice, the researchers produced depressed behavior. Inhibiting the activity of dopamine neurons in depressed mice eased their depression.

“Increasing evidence shows that depression may not only be caused by a chemical imbalance in the brain but also by neuronal misfiring in different areas brain,” said Dr. Chaudhury. “By targeting neurons in the reward center of the brain, we were able to demonstrate that this chemical may be a promising target for new treatments for depression.”

Innate Immune System Influences Vulnerability to Anxiety or Depression in Animal Model: October13

Scientists have hypothesized that depression results from an inflammatory response in the brain, indicating some immune system involvement. Led by Georgia Hodes, PhD, a Postdoctoral Fellow in the laboratory of Scott Russo, PhD, in the Department of Neuroscience at Mount Sinai, a team of researchers tested this hypothesis by evaluating a cytokine called interleukin-6, which is a protein released by white blood cells in response to injury and is found in elevated levels in people with treatment-resistant depression. They found no evidence of interleukin-6 being made in the brain areas examined, suggesting that it is released in the peripheral immune system.

Next, the Mount Sinai team transplanted the bone marrow of depressed mice into healthy mice and found that these previously healthy mice exhibited signs of depression after experiencing a mild stressor. They also found that mice with immune cells that release more interleukin-6 in response to a toxin developed a more severe depression-like response to the stress.

“To our knowledge, this is the first study showing a functional role for the peripheral immune system in an animal model of depression,” said Dr. Hodes. “This study suggests that cytokine-based antibody therapy currently approved for treatment of inflammatory illnesses such as rheumatoid arthritis and Castleman’s disease in humans may have potential as an antidepressant treatment.”

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Other researchers involved in Dr. Hodes work include Miriam Merad, PhD, Marilyn Lebouef, MS, and graduate students Madeline Pfau, Daniel Christoffel, Sam Golden, and MD/PhD student Mitra Heshmati.
Dr. Chaudhury’s research was supported by the National Institute of Mental Health and a Johnson & Johnson/IMHRO Rising Star Translational Research Award.
Dr. Hodes’ research was supported by the National Institute of Mental Health, Johnson & Johnson/IMHRO Rising Star Translational Research Award, and an institutional training grant from the National Institute on Drug Abuse.The Mount Sinai Hospital / Mount Sinai School of Medicine